These studies are directed at understanding the quantitative and qualitative interactions of antitumor agents with target sites in tumor cells. Emphasis has been placed on understanding factors which determine response to antifolates, 5-fluorouracil, and the pineal hormone, melatonin, at the cellular and biochemical level. In vitro uptake, binding to receptor sites, and cytotoxicity of these agents are examined in tissue culture systems as well as in the whole animal.